Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Influence of deficit irrigation and crop load on the yield and fruit quality in Wonderful and Mollar de Elche pomegranates

BACKGROUND The working hypothesis of the present study was that, by proper simultaneous control of irrigation (hydroSOStainable products) and crop load (thinning), it is possible to promote the accumulation of bioactive compounds and improve fruit appearance (size and weight). The effects of (i) irrigation status [T0, 120% ETc (estimated crop evapotranspiration); T1, 60% ETc during fruit growth and ripening] and (ii) crop load (A0, no thinning; A1, thinning) on yield and fruit quality were evaluated in two pomegranate cultivars (Wonderful, Wond and Mollar de Elche, ME). RESULTS Thinning was effective in increasing the size and weight of fruits. Unfortunately, neither punicalagin, nor total polyphenolic content were positively affected by irrigation and thinning. T1A1 Wond fruits were characterized by high sugar content (glucose and fructose), together with high fruit size and weight. Furthermore, T1A1 ME fruits were characterized by high contents of alcohols and monoterpenoids (providing vegetal and citric flavor notes) and key sensory attributes (color, fruity and fresh pomegranate). CONCLUSION The final recommendation was to use the treatment T1A1 [simultaneous combination of deficit irrigation during fruit growth and ripening (T1) and thinning (A1)], although the positive results were cultivar-dependent

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease